POS1327 HORMONE REPLACEMENT THERAPY INCREASES THE RISK OF SYSTEMIC SCLEROSIS: RESULTS FROM LARGE POPULATION-BASED CASE-CONTROL STUDY
Authors: K. Patasova, M. Dehara, E. Arkema, M. Holmqvist
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic sclerosis (SSc) exhibits, similarly to other autoimmune diseases, a strong female preponderance. Estrogen has been found to activate signaling pathways involved in immune response and promote autoimmunity [1]. Several studies on cultured SSc skin fibroblasts have reported fibrinogenic role of female sex steroids, but the hormonal impact on the risk of SSc remains underexplored. In a recently published pharmacovigilance report, hormone replacement therapy (HRT) was highlighted as potentially implicated in SSc development [2]. <h3>Objectives</h3> In this case-control study, we aimed to assess the relationship between HRT and risk of SSc in a population-based cohort of SSc patients and matched controls. <h3>Methods</h3> Participants with newly diagnosed SSc and their matched controls were identified from nationwide registers. Definition of SSc required a first-time diagnosis of SSc (ICD10 codes: M34.0, M34.1, M34.9, M34.8, as a primary diagnosis) in specialist care, with a second visit listing SSc within 12 months We included visits between Jan 1, 2009 and December 31, 2017 with the first visit representing the index date. Controls were sex, age and region-matched to SSc cases in 1:5 ratio. Study sample was restricted to women aged 40 or older at index date. Participants on progestogen in monotherapy and those with history of thromboembolism, stroke, ischemic heart disease, endometrial and breast cancer before index date, were excluded. Dispensations of HRT were extracted from Prescription register, using The Anatomical Therapeutic Chemical classification system codes. Study participants with a history of ever taking HRT (estrogen, estrogen and progestogen combination and tibolone) at least three years before the index date were considered exposed. The relationship between HRT and SSc was assessed using conditional logistic regression models adjusted for socioeconomic factors and polypharmacy. The impact of underlying comorbidities was evaluated by identifying the most common ICD-10 codes among the users of HRT and sequentially excluding cases and controls with a history of these comorbidities from the analyses. <h3>Results</h3> In total, 553 SSc cases and 2,696 controls were included. Twelve percent of cases and 9% of controls were taking HRT at any time ≥3 years before the index date was associated with a 42% increased risk of SSc (95% CI: 1.1,1.9; p=0.02, Figure 1 a). Combination of estrogen and progestogen showed statistically significant associations with SSc (OR=1.5; 95% CI: 1.0,2.05; p=0.03) (Figure 1 a). Subsequent sensitivity analyses indicated that underlying comorbidities did not influence the observed relationship between HRT and SSc (Figure 1 b). <h3>Conclusion</h3> The findings of this study implicate HRT in the development of SSc and add to a growing body of evidence pointing to the proinflammatory role of female sex steroids in the pathogenesis of immune-mediated disorders. <h3>References</h3> [1]Ciaffi J, van Leeuwen NM, Schoones JW, Huizinga TWJ, de Vries-Bouwstra JK. Sex hormones and sex hormone-targeting therapies in systemic sclerosis: A systematic literature review. Semin Arthritis Rheum. 2020 Feb 1;50(1):140–8. [2]Dumont A, Dolladille C, de Boysson H, Alexandre J, Nguyen A, Deshayes S, et al. Drugs associated with systemic sclerosis: An updated list of suspected drugs using the WHO pharmacovigilance database. Autoimmun Rev. 2022 Sep 1;21(9):103157. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.